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Journal of Virology, April 2005, p. 4382-4395, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4382-4395.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Effects of Foot-and-Mouth Disease Virus Nonstructural Proteins on the Structure and Function of the Early Secretory Pathway: 2BC but Not 3A Blocks Endoplasmic Reticulum-to-Golgi Transport

Katy Moffat,1,{dagger} Gareth Howell,1,{dagger} Caroline Knox,2 Graham J. Belsham,1 Paul Monaghan,1 Martin D. Ryan,2 and Thomas Wileman1*

Pirbright Laboratory, BBSRC Institute for Animal Health, Pirbright, Surrey,1 School of Biology, Centre for Biomolecular Sciences, University of St. Andrews, North Haugh, St. Andrews, United Kingdom2

Received 12 July 2004/ Accepted 23 November 2004

Infection of cells by picornaviruses leads to the generation of intracellular membrane vesicles. The expression of poliovirus (PV) 3A protein causes swelling of the endoplasmic reticulum (ER) and inhibition of protein trafficking between the ER and the Golgi apparatus. Here, we report that the nonstructural proteins of a second picornavirus, foot-and-mouth disease virus (FMDV), also perturb the secretory pathway. FMDV proteins 3A, 2B, 2C, and 2BC expressed alone in cells were recovered from crude membrane fractions, indicating membrane association. Immunofluorescence microscopy showed that 3A was located in a reticular structure and 2B was located in the ER, while 2C was located in both the ER and the bright punctate structures within the Golgi apparatus. 2BC gave punctate cytoplasmic staining and also caused accumulation of ER proteins in large vesicular structures located around the nuclei. The effect of the FMDV proteins on the trafficking of the vesicular stomatitis virus glycoprotein (G protein) from the ER to the cell surface was determined. Unlike its PV counterpart, the 3A protein of FMDV did not prevent trafficking of the G protein to the cell surface. Instead, surface expression of the G protein was blocked by 2BC, with retention of the G protein in a modified ER compartment staining for 2BC. The results suggest that the nonstructural proteins of different picornaviruses may vary in their ability to perturb the secretory pathway. Since FMDV 2BC can block the delivery of proteins to the cell surface, it may, as shown for PV 3A, play a role in immune evasion and contribute to the persistent infections observed in ruminants.

* Corresponding author. Mailing address: Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Surrey GU24 0NF, United Kingdom. Phone: 44 01483 232441. Fax: 44 01483 232448. E-mail: thomas.wileman{at}bbsrc.ac.uk.

{dagger} K.M. and G.H. contributed equally to this work.

Journal of Virology, April 2005, p. 4382-4395, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4382-4395.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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